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Combination of 5-azacitidine and Lenalidomide in Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) Myelodysplastic Syndromes

Information source: Technische Universität Dresden
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myelodysplastic Syndromes; Acute Myelogenous Leukemia

Intervention: Azacitidine (Drug); Lenalidomide (Drug)

Phase: Phase 1

Status: Terminated

Sponsored by: Technische Universität Dresden

Official(s) and/or principal investigator(s):
Uwe Platzbecker, MD, Principal Investigator, Affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus

Summary

The hypothesis of this study is that 5-aza and lenalidomide act synergistically in MDS and AML patients with chromosomal abnormalities involving monosomy 5 or del5q. Therefore, this phase I study will investigate the maximum tolerated dose (MTD) of lenalidomide in combination with a fixed dose of 5-aza in this patient population.

Clinical Details

Official title: A Phase I Study of a Combination of 5-azacitidine Followed by Lenalidomide in High-risk MDS or Relapsed/Refractory AML Patients With Cytogenetic Abnormalities Including -5 or Del(5q)

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine)

Secondary outcome:

Clinical and cytogenetic response

Safety (type, frequency, severity, and relationship of adverse events to study treatment)

Detailed description: Cytogenetics are the main predictors of outcome in patients with AML. In fact, a monosomy 5 or del (5q) as single aberration are poor prognostic markers. Overall, the complete response rate for conventionally treated patients with newly-diagnosed AML with chromosome 5 abnormalities is about 31% to 37 % and all patients rapidly relapse if not rescued by allogeneic HSCT. The situation is almost similar in patients with high-risk MDS. Vidaza® has been shown in clinical trials to achieve remission rates in about 29% (CR+PR) of the patients while a total of 49% achieve improvement of blood counts. Revlimid® is also able to achieve complete remissions in advanced MDS and even overt leukemia with or without chromosome 5 abnormalities. Nevertheless, response rates are lower compared to low-risk MDS (IPSS Low/INT-1). Therefore, Revlimid® seems to be too weak as a single agent, but a promising compound for a combination therapy.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Understand and voluntarily sign an informed consent form.

- Age >=18 years at the time of signing the informed consent form.

- Able to adhere to the study visit schedule and other protocol requirements.

- Relapsed or refractory AML (>30% blasts, FAB classification)with karyotype

abnormalities involving monosomy 5 or del(5q) or MDS and t-MDS INT-2 or HIGH according to IPSS classification with karyotype abnormalities involving monosomy 5 or del(5q) either previously treated or untreated

- Not eligible for an immediate allogeneic HSCT (due to donor unavailability)

- All previous MDS or AML specific therapy with exception of corticosteroids not

exceeding doses of 10mg/day prednisone must have been discontinued at least 1 week prior to study enrollment.

- Non-hematological toxicity (except alopecia) resulting from previous treatment must

be resolved to WHO CTC Grade ≤ 2.

- ECOG performance status of < 3 at study entry.

- Laboratory test results within these ranges: Serum creatinine <= 2. 0 mg/dL, Total

bilirubin <= 3 x ULN, AST (SGOT) and ALT (SGPT) <= 3 x ULN

- Females of childbearing potential must agree to use a reliable form of contraception

or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that

would prevent the subject from signing the informed consent form.

- Pregnant or breast feeding females. (Lactating females must agree not to breast feed

while on study).

- Any condition, including the presence of laboratory abnormalities, which places the

subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

- Known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol.

- Myocardial infarction within 6 months before study entry, New York Heart Association

Class III or IV heart failure, uncontrolled angina or severe uncontrolled ventricular arrhythmias.

- The development of erythema nodosum if characterized by a desquamating rash while

taking thalidomide or similar drugs.

- Uncontrolled lung disease.

- Known positive for HIV or acute infectious hepatitis, type A, B or C.

- Participation in another clinical study in the 4 weeks prior to enrollment or during

this study.

Locations and Contacts

Medizinische Klinik und Poliklinik I, Uniklinik, Dresden, Germany

Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie, Düsseldorf 40225, Germany

Klinikum der J.W. Goethe-Universität, Medizinische Klink II, Frankfurt 60590, Germany

Technische Universität München, Klinikum Rechts der Isar, München 81675, Germany

Additional Information

Starting date: June 2009
Last updated: December 17, 2013

Page last updated: August 23, 2015

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